Chlamydia, caused by the bacterium Chlamydia trachomatis, is one of the most important sexually-transmitted infections globally. In addition to accounting for millions of cases every year, the disease causes numerous irreversible complications such as chronic pelvic pain, infertility in females and pelvic inflammatory disease. This thesis presents a number of mathematical models, of the form of deterministic systems of non-linear differential equations, for gaining qualitative insight into the transmission dynamics and control of Chlamydia within an infected host (in vivo) and in a population. The models designed address numerous important issues relating to the transmission dynamics of Chlamydia trachomatis, such as the roles of immune response, sex structure, time delay (in modelling the latency period) and risk structure (i.e., risk of acquiring or transmitting infection). The in-host model is shown to have a globally-asymptotically stable Chlamydia-free equilibrium whenever a certain biological threshold is less than unity. It has a unique Chlamydia-present equilibrium when the threshold exceeds unity. Unlike the in-host model, the two-group (males and females) population-level model undergoes a backward bifurcation, where a stable disease-free equilibrium co-exists with one or more stable endemic equilibria when the associated reproduction number is less than unity. This phenomenon, which is shown to be caused by the re-infection of recovered individuals, makes the effort to eliminate the disease from the population more difficult. Extending the two-group model to incorporate risk structure shows that the backward bifurcation phenomenon persists even when recovered individuals do not acquire re-infection. In other words, it is shown that stratifying the sexually-active population in terms of risk of acquiring or transmitting infection guarantees the presence of backward bifurcation in the transmission dynamics of Chlamydia in a population. Finally, it is shown (via numerical simulations) that a future Chlamydia vaccine that boosts cell-mediated immune response will be more effective in curtailing Chlamydia burden in vivo than a vaccine that enhances humoral immune response. The population-level impact of various targeted treatment strategies, in controlling the spread of Chlamydia in a population, are compared. In particular, it is shown that the use of treatment could have positive or negative population-level impact (depending on the sign of a certain epidemiological threshold).

Chlamydia, caused by the bacterium Chlamydia trachomatis, is one of the most important sexually-transmitted infections globally. In addition to accounting for millions of cases every year, the disease causes numerous irreversible complications such as chronic pelvic pain, infertility in females and pelvic inflammatory disease. This thesis presents a number of mathematical models, of the form of deterministic systems of non-linear differential equations, for gaining qualitative insight into the transmission dynamics and control of Chlamydia within an infected host (in vivo) and in a population. The models designed address numerous important issues relating to the transmission dynamics of Chlamydia trachomatis, such as the roles of immune response, sex structure, time delay (in modelling the latency period) and risk structure (i.e., risk of acquiring or transmitting infection). The in-host model is shown to have a globally-asymptotically stable Chlamydia-free equilibrium whenever a certain biological threshold is less than unity. It has a unique Chlamydia-present equilibrium when the threshold exceeds unity. Unlike the in-host model, the two-group (males and females) population-level model undergoes a backward bifurcation, where a stable disease-free equilibrium co-exists with one or more stable endemic equilibria when the associated reproduction number is less than unity. This phenomenon, which is shown to be caused by the re-infection of recovered individuals, makes the effort to eliminate the disease from the population more difficult. Extending the two-group model to incorporate risk structure shows that the backward bifurcation phenomenon persists even when recovered individuals do not acquire re-infection. In other words, it is shown that stratifying the sexually-active population in terms of risk of acquiring or transmitting infection guarantees the presence of backward bifurcation in the transmission dynamics of Chlamydia in a population. Finally, it is shown (via numerical simulations) that a future Chlamydia vaccine that boosts cell-mediated immune response will be more effective in curtailing Chlamydia burden in vivo than a vaccine that enhances humoral immune response. The population-level impact of various targeted treatment strategies, in controlling the spread of Chlamydia in a population, are compared. In particular, it is shown that the use of treatment could have positive or negative population-level impact (depending on the sign of a certain epidemiological threshold).

Deterministic models for the transmission dynamics of HIV/AIDS and trichomonas vaginalis (TV) in a human population are formulated and analysed. The models which assumed standard incidence formulations are shown to have globally asymptotically stable (GAS) disease-free equilibria whenever their associated reproduction number is less than unity. Furthermore, both models possess a unique endemic equilibrium that is GAS whenever the associated reproduction number is greater than unity. An extended model for the co-infection of TV and HIV in a human population is also designed and rigorously analysed. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium (DFE) co-exists with a stable endemic equilibrium whenever the associated reproduction number is less than unity. This phenomenon can be removed by assuming that the co-infection of individuals with HIV and TV is negligible. Furthermore, in the absence of co-infection, the DFE of the model is shown to be GAS whenever the associated reproduction number is less than unity. This study identifies a sufficient condition for the emergence of backward bifurcation in the model, namely TV-HIV co-infection. The endemic equilibrium point is shown to be GAS (for a special case) when the associated reproduction number is greater than unity. Numerical simulations of the model, using initial and demographic data, show that increased incidence of TV in a population increases HIV incidence in the population. It is further shown that control strategies, such as treatment, condom-use and counselling of individuals with TV symptoms, can lead to the effective control or elimination of HIV in the population if their effectiveness level is high enough. / Dissertation (MSc)--University of Pretoria, 2017. / DST-NRF SARChI Chair in Mathematical Models and Methods in Biosciences and Bioengineering (M3B2) / Mathematics and Applied Mathematics / MSc / Unrestricted

Seasonal and non-seasonal Susceptible-Exposed-Infective-Recovered-Susceptible (SEIRS) models are formulated and analyzed. It is proved that the disease-free steady state of the non-seasonal model is locally asymptotically stable if Rv < 1, and disease invades if Rv > 1. For the seasonal SEIRS model, it is shown that the disease-free periodic solution is locally asymptotically stable when R̅v < 1, and I(t) is persistent with sustained oscillations when R̅v > 1. Numerical simulations indicate that the orbit representing I(t) decays when R̅v < 1 < Rv. The seasonal SEIRS model with routine and pulse vaccination is simulated, and results depict an unsustained decrease in the maximum of prevalence of infectives upon the introduction of routine vaccination and a sustained decrease as pulse vaccination is introduced in the population. Mortality data of pneumonia and influenza is collected and analyzed. A decomposition of the data is analyzed, trend and seasonality effects ascertained, and a forecasting strategy proposed.

O fenômeno do aumento global da temperatura é uma realidade inquestionável. Tendo em vista tal cenário, acredita-se que haverá uma expansão geográfica (migração de populações humanas) e um aumento na incidência de infecções tropicais. No entanto, a tendência de aumento da severidade destas infecções como função do aumento da temperatura ainda é desconhecida. Suponha que duas cepas de um dado parasita estejam competindo pelo mesmo hospedeiro. É possível mostrar que, em geral, a cepa com uma estratégia evolu- cionária estável, isto é, aquela que vence a competição, é aquela com maior valor de reprodutibilidade basal. Queremos saber quais combinações de temperatura ambiental T e virulência V maximizam Ro(T, V). Para isto calculamos o plano tangente ao ponto máximo (ou a uma região de máximo) e analisamos as respectivas curvas de nível. Para tanto, calculamos o seguinte sistema de equações diferenciais: ?Ro/?T = 0 ; ?Ro/?V = 0 (1). Agora, consideremos o caso de uma infecção transmitida por um vetor. De- monstramos que, neste caso, o aumento na Virulência do parasita está associada ao aumento na Temperatura. Esta hipótese é embasada por evidências empíricas de dengue hemorrágica em Singapura que vem aumentando sua virulência à medida em que há um aumento observado da temperatura local nos últimos anos. / The phenomenon of global increase of the temperature is reality unquestionable. In this case, it is expected that the increase in the global temperature will lead to an expansion of the geographical spread and to an increase in the incidence of tropical infections. However, the trend in severity of those infections as a function of the increase in the temperature is still unknown. Suppose that two strains of a given parasite are competing for the same host. It is possible to demonstrate that, in general, the strain with an evolutionary stable strategy, that is, the one that wins the competition, is the one with the highest value of R 0. We want to know which combination of environmental temperature T and virulence V maximizes R 0( V ). For this we calculate the tangent plane to the maximum point, that is ?Ro/?T=0 ; ?Ro/?V=0 (2) Now, let us consider the case of a vector-borne infection. We demonstrate, in this case, that the increase in temperature is associated with an increase in the parasite virulence. This hypothesis is supported by empirical evidence from dengue hemorrhagic fever in Singapore, which is increasing its virulence along with the increase in the local temperature observed in the last years.

Les infections à Papillomavirus Humain (HPV) sont des infections sexuellement transmissibles très fréquentes. La persistance de ces infections est un facteur causal du cancer du col de l’utérus et est aussi à l’origine d’autres cancers de la zone ano-génitale et de verrues génitales chez les femmes et chez les hommes. Depuis l’introduction de deux vaccins bivalent et quadrivalent permettant de prévenir certains types d’HPV, de nombreux modèles mathématiques ont été développés afin d’estimer l’impact potentiel de différentes stratégies de vaccination. L’objectif de ce travail de thèse a été d’estimer l’impact potentiel de la vaccination en France sur l’incidence de certains cancers liés à l’HPV, notamment le cancer du col de l’utérus et le cancer anal chez les femmes françaises ; ainsi que sur la prévalence des infections à HPV 6/11/16/18. Différents modèles dynamiques de type déterministe ont été développés. Ils sont représentés par des systèmes d’équations différentielles ordinaires. Une étude théorique du comportement asymptotique d’un premier modèle comportant peu de strates a été réalisée. Le nombre de reproduction de base R0 et le nombre de reproduction avec vaccination Rv ont été estimés. Des modèles plus complexes ont intégré une structure d’âge et de comportement sexuel. Les modélisations réalisées permettent de conclure à l’impact important de la vaccination sur la prévalence des infections à HPV et sur l’incidence des cancers du col de l’utérus et de la zone anale chez les femmes françaises dans un délai de quelques décennies, si l’on prend en compte les taux de vaccination observés en France au début de la campagne de vaccination / Human Papillomavirus infection (HPV) is the most frequent sexually transmitted disease. Epidemiological studies have established a causal relationship between HPV infections and occurence of cervical cancer. These infections have also been incriminated in anogenital cancers and anogenital warts among women and men. Since the introduction of bivalent and quadrivalent vaccines which offer protection against some HPV genotypes, many mathematical models have been developed in order to assess the potential impact of vaccine strategies. The aim of this thesis work was to assess the potential impact of HPV vaccination in France on the incidence of some cancers linked with HPV, particularly cervical cancer and anal cancer in French women, and on the prevalence of HPV 6/11/16/18 infections. Different deterministic dynamic models have been developped. They are represented by systems of ordinary differential equations. A theoretical analysis of the asymptotic behavior for a first model with few strata is realized. The basic reproduction number R0 and the vaccinated reproduction number Rv are assessed. More complex models taking into account age and sexual behavior have been developed. Using vaccination rates observed in France at the launch of the vaccination campaign, our modeling shows the large impact of vaccination on HPV prevalences, on cervical cancer and anal cancer incidences among French women within a few decades

O fenômeno do aumento global da temperatura é uma realidade inquestionável. Tendo em vista tal cenário, acredita-se que haverá uma expansão geográfica (migração de populações humanas) e um aumento na incidência de infecções tropicais. No entanto, a tendência de aumento da severidade destas infecções como função do aumento da temperatura ainda é desconhecida. Suponha que duas cepas de um dado parasita estejam competindo pelo mesmo hospedeiro. É possível mostrar que, em geral, a cepa com uma estratégia evolu- cionária estável, isto é, aquela que vence a competição, é aquela com maior valor de reprodutibilidade basal. Queremos saber quais combinações de temperatura ambiental T e virulência V maximizam Ro(T, V). Para isto calculamos o plano tangente ao ponto máximo (ou a uma região de máximo) e analisamos as respectivas curvas de nível. Para tanto, calculamos o seguinte sistema de equações diferenciais: ?Ro/?T = 0 ; ?Ro/?V = 0 (1). Agora, consideremos o caso de uma infecção transmitida por um vetor. De- monstramos que, neste caso, o aumento na Virulência do parasita está associada ao aumento na Temperatura. Esta hipótese é embasada por evidências empíricas de dengue hemorrágica em Singapura que vem aumentando sua virulência à medida em que há um aumento observado da temperatura local nos últimos anos. / The phenomenon of global increase of the temperature is reality unquestionable. In this case, it is expected that the increase in the global temperature will lead to an expansion of the geographical spread and to an increase in the incidence of tropical infections. However, the trend in severity of those infections as a function of the increase in the temperature is still unknown. Suppose that two strains of a given parasite are competing for the same host. It is possible to demonstrate that, in general, the strain with an evolutionary stable strategy, that is, the one that wins the competition, is the one with the highest value of R 0. We want to know which combination of environmental temperature T and virulence V maximizes R 0( V ). For this we calculate the tangent plane to the maximum point, that is ?Ro/?T=0 ; ?Ro/?V=0 (2) Now, let us consider the case of a vector-borne infection. We demonstrate, in this case, that the increase in temperature is associated with an increase in the parasite virulence. This hypothesis is supported by empirical evidence from dengue hemorrhagic fever in Singapore, which is increasing its virulence along with the increase in the local temperature observed in the last years.

Ce travail de thèse traite de la modélisation et du contrôle des maladies infectieuses à l’aide des automates cellulaires. Nous nous sommes d’abord focalisés sur l’étude d’un modèle de type SEIR. Nous avons pu monter d’une part qu’un voisinage fixe pouvait entrainer une sous-évaluation de l’incidence et de la prévalence et d’autre part que sa structure a un impact direct sur la structure de la distribution de la maladie. Nous nous sommes intéressés également la propagation des maladies vectorielles à travers un modèle de type SIRS-SI multi-hôtes dans un environnement hétérogène.Les hôtes y étaient caractérisés par leur niveau de compétence et l’environnement par la variation du taux de reproduction et de mortalité. Son application à la maladie de Chagas, nous a permis de montrer que l’hétérogénéité de l’habitat et la diversité des hôtes contribuaient à faire baisser l’infection. Cependant l’un des principaux résultats de notre travail à été la formulation du nombre de reproduction spatiale grâce à deux matrices qui représentent les coefficients d’interactions entre les différentes cellules du réseau. / This PhD thesis considers the general problem of epidemiological modelling and control using cellular automata approach.We first focused on the study of the SEIR model. On the one hand, we have shown that the traditionnal neighborhood contribute to underestimate the incidence and prevalence of infection disease. On the other hand, it appeared that the spatial distribution of the cells in the lattice have a real impact on the disease spreading. The second study concerns the transmission of the vector-borne disease in heterogeneous landscape with host community. We considered a SIRS-SI with various level of competence at witch the environnment heterogeneity has been characterized by the variation of the birth flow and the death rate. We simulated the Chagas disease spreading and shown that the heterogeneity of habitat and host diversity contribute to decrease the infection. One of the most important results of our work, was the proposition of the spatial reproduction number expression based on two matrices that represent the interaction factors between the cells in the lattice.

abstract: The role of climate change, as measured in terms of changes in the climatology of geophysical variables (such as temperature and rainfall), on the global distribution and burden of vector-borne diseases (VBDs) remains a subject of considerable debate. This dissertation attempts to contribute to this debate via the use of mathematical (compartmental) modeling and statistical data analysis. In particular, the objective is to find suitable values and/or ranges of the climate variables considered (typically temperature and rainfall) for maximum vector abundance and consequently, maximum transmission intensity of the disease(s) they cause. Motivated by the fact that understanding the dynamics of disease vector is crucial to understanding the transmission and control of the VBDs they cause, a novel weather-driven deterministic model for the population biology of the mosquito is formulated and rigorously analyzed. Numerical simulations, using relevant weather and entomological data for Anopheles mosquito (the vector for malaria), show that maximum mosquito abundance occurs when temperature and rainfall values lie in the range [20-25]C and [105-115] mm, respectively. The Anopheles mosquito ecology model is extended to incorporate human dynamics. The resulting weather-driven malaria transmission model, which includes many of the key aspects of malaria (such as disease transmission by asymptomatically-infectious humans, and enhanced malaria immunity due to repeated exposure), was rigorously analyzed. The model which also incorporates the effect of diurnal temperature range (DTR) on malaria transmission dynamics shows that increasing DTR shifts the peak temperature value for malaria transmission from 29C (when DTR is 0C) to about 25C (when DTR is 15C). Finally, the malaria model is adapted and used to study the transmission dynamics of chikungunya, dengue and Zika, three diseases co-circulating in the Americas caused by the same vector (Aedes aegypti). The resulting model, which is fitted using data from Mexico, is used to assess a few hypotheses (such as those associated with the possible impact the newly-released dengue vaccine will have on Zika) and the impact of variability in climate variables on the dynamics of the three diseases. Suitable temperature and rainfall ranges for the maximum transmission intensity of the three diseases are obtained. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics 2018

>Magister Scientiae - MSc / HIV/AIDS is nowadays considered as the greatest public health disaster of modern time. Its progression has challenged the global population for decades. Through mathematical modelling, researchers have studied different interventions on the HIV pandemic, such as treatment, education, condom use, etc. Our research focuses on different compartmental models with emphasis on the effect of public health education. From the point of view of statistics, it is well known how the public health educational programs contribute towards the reduction of the spread of HIV/AIDS epidemic. Many models have been studied towards understanding the dynamics of the HIV/AIDS epidemic. The impact of ARV treatment have been observed and analysed by many researchers. Our research studies and investigates a compartmental model of HIV with treatment and education campaign. We study the existence of equilibrium points and their stability. Original contributions of this dissertation are the modifications on the model of Cai et al. [1], which enables us to use optimal control theory to identify optimal roll-out of strategies to control the HIV/AIDS. Furthermore, we introduce randomness into the model and we study the almost sure exponential stability of the disease free equilibrium. The randomness is regarded as environmental perturbations in the system. Another contribution is the global stability analysis on the model of Nyabadza et al. in [3]. The stability thresholds are compared for the HIV/AIDS in the absence of any intervention to assess the possible community benefit of public health educational campaigns. We illustrate the results by way simulation The following papers form the basis of much of the content of this dissertation, [1 ] L. Cai, Xuezhi Li, Mini Ghosh, Boazhu Guo. Stability analysis of an HIV/AIDS epidemic model with treatment, 229 (2009) 313-323. [2 ] C.P. Bhunu, S. Mushayabasa, H. Kojouharov, J.M. Tchuenche. Mathematical Analysis of an HIV/AIDS Model: Impact of Educational Programs and Abstinence in Sub-Saharan Africa. J Math Model Algor 10 (2011),31-55. [3 ] F. Nyabadza, C. Chiyaka, Z. Mukandavire, S.D. Hove-Musekwa. Analysis of an HIV/AIDS model with public-health information campaigns and individual with-drawal. Journal of Biological Systems, 18, 2 (2010) 357-375. Through this dissertation the author has contributed to two manuscripts [4] and [5], which are currently under review towards publication in journals, [4 ] G. Abiodun, S. Maku Vyambwera, N. Marcus, K. Okosun, P. Witbooi. Control and sensitivity of an HIV model with public health education (under submission). [5 ] P.Witbooi, M. Nsuami, S. Maku Vyambwera. Stability of a stochastic model of HIV population dynamics (under submission).